Project Summary ADHD is defined by behavioral symptoms that are not well defined in relation to underlying neurobiology or mechanism. Using mechanisms to define its nosology and predict outcome is expected to be more powerful than the current approach, but this hope has not been realized. The current proposal seeks to break this impasse. It combines cognitive and emotion measures in a longitudinal design to establish (a) what mechanisms predict different outcomes, (b) whether novel, mechanism based types can be validated that will be useful to nosology and clinical practice, and (c) creation and cross validation of a clinical risk index that can directly translate mechanism knowledge into clinical practice. Although the rationale involves neurobiology to some extent, the measures are deliberately restricted to relatively low cost and easily disseminated measures that would readily be usable in clinical practice in a range of setting. A cohort of 486 children of which over 300 had well characterized ADHD at baseline will now be followed into adolescence in an accelerated longitudinal design. Over 2500 observations will be made across multiple waves and these will be used to characterize risk, recovery, and mechanisms. The project rationale and hypotheses derive from a detailed theoretical conception that the PI has developed over several years. The significance of the proposal derives from the potential to move ADHD mechanisms from theory to application both in nosology and clinical prediction. The innovation lies heavily in the proposal that mechanism based typology of ADHD is tractable and can be developed in a formal way. The approach will validate mechanism effects using a detailed longitudinal design that will enable strong evaluation of age and time invariance/dependence of both typing models and effect sizes of their predictive utility. The age range studied (childhood to middle adolescence) is ideal for examining persistence/desistance of ADHD as well as initiation of serious outcomes like drug use, health problems, and comorbid psychiatric disorders. Aim 1 will use a standard analytic strategy to evaluate mechanisms from a variable centered perspective. Aim 2 will use clustering validation approaches to explore the taxonomic possibilities of mechanism-based types and validate them over time. Aim 3 will introduce the risk score index to ADHD based on combining mechanisms and clinical features at different levels of analysis, with built in cross validation. The Aims directly match key priorities of the NIMH strategic plan. If successful, the project hopes to break the impasse facing the field with regard to utilizing mechanism-based concepts of ADHD in relation to taxonomy and clinical assessment.